Analyzing EEG and MEG signals recorded during tES, a reply

Highlights

• Explanation of the physics underlying tES artifacts.

• Rejection of all concerns raised by Neuling et al. (2017).

• Suggestion of several approaches to study brain activity with EEG or MEG during tES.

Abstract

Transcranial Electric Stimulation (tES) is a widely used non-invasive brain stimulation technique. However, strong stimulation artifacts complicate the investigation of neural activity with EEG or MEG during tES. Thus, studying brain signals during tES requires detailed knowledge about the properties of these artifacts. Recently, we characterized the phase- and amplitude-relationship between tES stimulation currents and tES artifacts in EEG and MEG and provided a mathematical model of these artifacts (Noury and Siegel, 2017, and Noury et al., 2016, respectively). Among several other features, we showed that, independent of the stimulation current, the amplitude of tES artifacts is modulated time locked to heartbeat and respiration. In response to our work, a recent paper (Neuling et al., 2017) raised several points concerning the employed stimulation device and methodology. Here, we discuss these points, explain potential misunderstandings, and show that none of the raised concerns are applicable to our results. Furthermore, we explain in detail the physics underlying tES artifacts, and discuss several approaches how to study brain function during tES in the presence of residual artifacts.

Introduction

Transcranial Electric Stimulation (tES) is a noninvasive brain stimulation technique that is widely used to manipulate brain function (Fertonani and Miniussi, 2016, Kuo and Nitsche, 2012). However, the neurophysiological mechanisms underlying tES effects are largely unknown, mainly because strong stimulation artifacts render the electrophysiological investigation of brain activity with EEG or MEG during tES challenging (Bergmann et al., 2016, Thut et al., 2017). Such simultaneous measurements may not only provide insights into the mechanisms underlying tES effects, but may also pave the way for new feedback-controlled brain stimulation protocols, in which stimulation parameters are continuously optimized based on the simultaneously recorded brain activity (Bergmann et al., 2016, Brittain et al., 2013, Lustenberger et al., 2016, Romei et al., 2016).

Despite several efforts to remove tES artifacts from simultaneously recorded EEG and MEG signals, a comprehensive artifact-removal pipeline that completely removes artifacts is still missing (Helfrich et al., 2014, Neuling et al., 2015, Soekadar et al., 2013, Voss et al., 2014). This is at least partly because the employed methods have been designed and used without considering the properties of tES artifacts. Recently, we characterized both, amplitude (Noury et al., 2016) and phase (Noury and Siegel, 2017) properties of tES artifacts for EEG and MEG. We suggested a mathematical model for the transfer function that defines the relationship between the stimulation current and tES artifacts and may be used for simulating tES artifacts (Noury and Siegel, 2017). We showed that the mapping between stimulation current and tES artifacts is non-linear and time-varying. The non-linearity manifests itself in the amplitude and phase of stimulation artifacts. Moreover, both, phase and amplitude of artifacts are rhythmically modulated time-locked to heartbeats and respiration, due to body resistance changes and head movements. These modulations have a time-varying spatial pattern, which makes the transfer function time-varying. We used the rhythmic modulation of artifact amplitudes as landmarks of tES artifacts to quantify their bandwidth in the frequency domain, and to detect the presence of artifacts at different stages of available artifact-removal pipelines. We showed that none of the available artifact-removal pipelines is able to completely remove stimulation artifacts. Therefore, we concluded that residual artifacts need to be considered to prevent false positive results and wrong conclusions (Noury et al., 2016).

In response to our work regarding the amplitude of tES artifacts (Noury et al., 2016), a recent paper (Neuling et al., 2017) raised several concerns. First, Neuling et al. argued that the amplitude modulations reported by us were due to a malfunction of our stimulation device. Second, they suggested that wrong parameters in our beamforming pipeline led to residual artifacts in our source-level estimations. We suspect that these concerns may be based on a misunderstanding of our results and of the physics underlying tES artifacts, because several findings in our previous paper ruled out the raised concerns, and because the authors made both their claims without applying the critical analyses suggested in our paper to their data. Therefore, in section 3, we first discuss in detail the physics behind amplitude modulations of tES artifacts, explain our previous findings in more detail, and suggest methods to detect artifacts in raw and processed signals (Table 1). In section 4, we then systematically discuss all sections of Neuling et al. (2017) and show that none of the raised concerns are correct or relevant to our results. Finally, in section 5, we point out several approaches and directions on how brain signals recorded during tES can be studied (Table 1).